Background: Microdialysis studies of antibacterial tissue distribution in critically ill patients have sometimes led to results that were spectacular but inconsistent with basic pharmacokinetic concepts.
Objective: To conduct a study of imipenem distribution in the muscle of healthy volunteers and critical care patients in order to compare real-life data with theory.
Methods: Microdialysis catheters were placed into the quadriceps, and probe recoveries were determined individually in vivo using a retrodialysis-by-drug method. Unbound imipenem concentrations were determined by high-performance liquid chromatography in plasma ultrafiltrates and muscle dialysates, and submitted to noncompartmental pharmacokinetic analysis.
Results: Individual unbound imipenem concentrations in plasma and muscle extracellular fluid were virtually superimposed at any time, both in healthy volunteers and in critical care patients.
Conclusion: These new results are not consistent with previously published data obtained in similar conditions by another group, but they are in agreement with results previously obtained in rats, as well as being consistent with basic pharmacokinetic concepts.
Imipenem Unbind Concentration Critical Care Patient Cilastatin Microdialysis Catheter
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This work was funded by a grant (PHRC) from the French Ministère de l’Education Nationale et de la Recherche. The authors thank Pharsight Corporation (Mountain View, CA, USA) for free supply of WinNonlin 4.0.1 software through the Pharsight Academic License (PAL) program. The authors have no conflicts of interest that are directly relevant to the content of this study.
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